WASHINGTON — Close relatives of people with autism often have subtle differences in the way they move their eyes, researchers said on Monday in a finding that might help doctors better diagnose and treat the condition.

The differences would not be noticeable in everyday life but they strongly suggest that many components of autism are inherited, the University of Illinois at Chicago team said.

"What we hope these tests do is to identify subgroups of individuals or subgroups of families that have some sort of risk for autism," Matthew Mosconi, who worked on the study, said in a telephone interview.

"The eye movement differences are the same as the ones that we saw previously in the kids with autism. It is a way to get at the functioning of these specific brain systems that we think are part of the development of autism."

The tests Mosconi's team developed may also form the basis for treatment, and for predicting which patients might respond to specific treatments, he said.

"The differences that we found are very subtle. These are not the kinds of differences in eye movements that you would ever detect during conversation with someone," Mosconi said.

Autism is a complex and mysterious brain disorder usually diagnosed in early childhood. It is characterized by difficulties in social interaction and communication, ranging from mild to profound impairment.

Autism spectrum disorders are diagnosed in one in 110 children in the United States and affect four times as many boys as girls. Researchers agree there is a strong genetic component.

In June, the world's largest genetic scan of people with autism in their families found that many patients have their own unique pattern of genetic mutation, not necessarily inherited.

Mosconi's team tested the inherited traits by enrolling 57 parents or siblings of people with autism and comparing test results to 40 people with no autistic relatives.

"Family members reported more communication abnormalities and obsessive-compulsive behaviors than controls," Mosconi's team wrote in the Archives of General Psychiatry.

The eye tests have been shown in other studies to reflect which brain pathways are involved in some of the characteristic patterns seen in people with autism.

One test involved switching the gaze quickly to follow a light as it popped on and off, while another involved tracking a slow-moving object.

"We know a good amount of what actually is going on in the brain while people are doing these very simple tests," Mosconi said. "We can identify specific parts of the brain that don't seem to be functioning at the optimal level," Mosconi said.

The tests can help scientists identify the brain systems at work in autism, a very complex condition which varies from person to person, Mosconi said.

They could also help in the search for specific treatments. Behavioral therapy can help some very young children with autism, studies have shown.

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A detailed study of brain samples of children with autism who died young shows remarkably clear changes in their brains, researchers reported on Wednesday.
The differences are seen both on the genetic level and in the physical structure of the brain, and strongly support what scientists have been saying for years — that autism starts with disrupted genes that somehow interfere with brain development.

The changes look like patches of arrested development deep in the brain, says Eric Courchesne of the University of California, San Diego’s Autism Center of Excellence.
"They are actually jam-packed with brain cells," Courchesne told NBC News. Not only are there too many cells, but they are not developed properly. "Brain cells are there but they haven’t changed into the kind of cell they are supposed to be. It's a failure of early formation."
It supports the idea that the changes that cause autism are happening in the second and third trimester of pregnancy, Courchesne said.
"Brain cells are there but they haven’t changed into the kind of cell they are supposed to be. It's a failure of early formation."
But the findings also raise as many questions as they answer about the condition, which has been diagnosed with increasing frequency in the U.S. and elsewhere.
The physical changes suggest that something is causing autism that scientists had not identified before, but they don’t shed much light on what that new mechanism might be, Courchesne and colleagues wrote in their report, published in the New England Journal of Medicine.
Autism is becoming more and more common among U.S. kids, and researchers don’t quite understand why. The last survey by the Centers for Disease Control and Prevention showed 2 percent of U.S. children have been diagnosed with an autism spectrum disorder, which can range from the relatively mild social awkwardness of Asperger’s syndrome to profound mental retardation, debilitating repetitive behaviors and an inability to communicate.

There’s no cure and no good treatment.
Genetics are a large factor — if one twin has autism the other twin is very likely to — but genes don’t explain it all. Better diagnosis doesn’t explain all of it, either, and many scientists are looking at what happens in pregnancy. Some studies suggest that infections such as influenza during pregnancy may play a role.
Courchesne said his team's findings support the idea that both genes and some outside influence are working together to disrupt brain development. "It has to be something that involves mom, something that she is exposed to or that is happening to her," he said.
It’s already known that kids with autism have larger-than-normal brains. One hypothesis is that the growing brain of a child with autism doesn’t “prune” unneeded connections properly, and the resulting overgrowth of nerve connections sends the brain into overdrive.

"This also further reinforces the understanding that autism is caused by genetic factors, and the need to identify autism as early as possible, so that treatment can be started when they have the greatest potential."
For the latest study, Courchesne and colleagues got brain samples from 11 children with autism who died young, mostly from accidents such as drowning, when aged 2 to 15. They compared their samples to brain tissue of 11 kids without autism who also died suddenly.
To their surprise, they found extremely similar changes in 10 out of the 11 children with autism. They found “patches” of abnormal development in the tissue taken from the brain regions important for social development, communication and language. The visual cortex was unaffected.

"That means it’s common. That points to a common time, a common place. And that is startling," Courchesne said.
And the changes were deep in the brain, suggesting that they happened early in development.
“Building a baby’s brain during pregnancy involves creating a cortex that contains six layers,” Courchesne said. The defects were deep among these layers. "It's kind of like looking back in time," he said.
“Numerous brain imaging studies have revealed that ASD (autism spectrum disorder) can affect how the brain functions, but this study takes us to a new level by homing in on changes in the brain’s fundamental building blocks,” said David Smith, head of discovery research at Autism Speaks, which helps fund Courchesne’s work.
What flummoxed the researchers was that the 11 children with autism had a range of symptoms. Many couldn’t speak well and one did not speak at all. Some liked to watch videos quietly, while others showed the repetitive behavior that is one of the hallmarks of severe autism.
Yet the pattern of changes in their brains was very similar. It could be that autism is caused by specific genetic damage, and where that damage occurs affects behavior, the researchers said.
"One of the remarkable things about children with autism is even at young ages, many of them will have very similar degrees of social and language impairment, but some get better and some don't," Courchesne told NBC News.

"So it's always been a big mystery what's the basis for getting better and not getting better," he added. Maybe the brain can re-wire itself, depending on where the patches of damage are, he said.
"This also further reinforces the understanding that autism is caused by genetic factors, and the need to identify autism as early as possible, so that treatment can be started when they have the greatest potential," said Dr. Paul Wang, head of medical research at Autism Speaks.
And Dr. Deborah Fein of the University of Connecticut, who was not involved in the study, said the study shows why it's so important to donate tissue and organs for scientific study.Hayley Goldbach, the 2013–14 Stanford–NBC News Global Health and Media Fellow, Senior Medical Producer Erika Edwards and Senior Nightly News Researcher Judy Silverman contributed to this story.

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